We propose to continue a longitudinal study, underway since 1985, of current and former intravenous drug users of known HIV-antibody status enrolled in a methadone program in the Bronx, New York. The study has included the examination of HIV-related risk behaviors, AIDS and non-AIDS-defining disease outcomes, and laboratory parameters in both HIV seropositives and seronegatives. Over the last five years, we have: monitored the rate of and risk factors for HIV seroconversion; defined the spectrum of HIV-related disease and the rate of progression from asymptomatic HIV infection to symptomatic clinical disease; described the decline of immunologic parameters; and determined rates of disease outcomes and mortality. Factors related to drug use, sexual activity, knowledge of HIV status, and risk of heterosexual and perinatal HIV transmission have been explored. We will continue to define high-risk behaviors by refining current techniques and add ethnographic study of drug-using women. We propose to apply interventions to reduce high-risk behavior and improve clinical care in this cohort. We will increase the study sample size and continue to monitor disease outcomes as affected by therapeutic interventions. We propose to further study behavioral variables which affect access to and compliance with therapy, with the aim of fashioning and testing effective behavioral interventions. We will also investigate factors relating to utilization of medical resources. We propose to continue our collaboration with the ALIVE study in Baltimore to study intravenous drug users with known dates of seroconversion, in order to formulate a model to impute dates of seroconversion for the seroprevalent cohorts at both sites, thereby more precisely characterizing time from infection to various HIV disease outcomes. We propose to continue this study for five years, in order to be able to observe and fully describe the changing natural history of HIV infection as the epidemic matures and clinical interventions alter the course of HIV disease.